Temporary carbohydrate diol protection with ester groups - orthogonality under solid-phase oligosaccharide synthesis conditions

Article abstract of DOI:10.1002/ejoc.200900627

For regioselective deprotection studies under SPOS conditions the glucosamine derivatives 4ab/4ba, 4ac/4ca and 4ad/ 4da - with Fmoc/PA, Fmoc/Lev or Fmoc/Alloc, respectively, as temporary ester protecting groups at 3-O and A-O - were prepared. Fmoc cleavag

Full text of DOI:10.1002/ejoc.200900627

FULL PAPER
DOI: 10.1002/ejoc.200900627
Temporary Carbohydrate Diol Protection with Ester Groups – Orthogonality
under Solid-Phase Oligosaccharide Synthesis Conditions[‡]
Shankar D. Markad[a] and Richard R. Schmidt*[a]
Keywords: Protecting groups / Carbohydrates / Glucosamine / Diols, vicinal / Solid-phase synthesis / Oligosaccharides
For regioselective deprotection studies under SPOS condi-
tions the glucosamine derivatives 4ab/4ba, 4ac/4ca and 4ad/
4da – with Fmoc/PA, Fmoc/Lev or Fmoc/Alloc, respectively,
as temporary ester protecting groups at 3-O and 4-O – were
prepared. Fmoc cleavage with triethylamine in 4ab or 4ba
led to PA migration, so the Fmoc/PA pair does not permit
regioselective access to the vicinal hydroxy groups. Under
the same reaction conditions no Lev migration in 4ac/4ca or
Alloc migration in 4ad/4da was observed. Lev removal with
hydrazinium acetate in 4ac/4ca and Alloc removal with Pd0
and dimedone as nucleophile in 4ad/4da was also not ac-
companied by Fmoc migration, so the Fmoc/Lev pair and the
Fmoc/Alloc pair can be successfully employed for regioselec-
tive access to the 3-hydroxy or the 4-hydroxy group, respec-
tively. However, Fmoc cleavage with piperidine in 4ac/4ca
led to Lev migration, and the use of a basic nucleophile for
Alloc cleavage also led to Fmoc migration in 4ad. 4-O-Fmoc
protection was also combined with Nap ether protection in
4ea. These two groups could be readily and regioselectively
removed, thus providing another useful pair for temporary
protection of vicinal diols.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2009)
Introduction
Results and Discussion
The ester-based SPOS methodology, very successfully ap-
plied to the synthesis of branched N-glycans[17]
(Scheme 1, A), involves: (i) different types of esters as tem-
porary protecting groups [that is, the benzoate group as a
linker and for chain termination and the Fmoc and PA
(phenoxyacetyl) groups as temporary protecting groups for
chain extension and 3-O,6-O-branching at the mannosyl
residue c, respectively] that can be chemoselectively cleaved,
(ii) the benzyl group for permanent O-protection and for
the spacer between the anomeric centre at the reducing end
sugar, thus providing a structurally defined target molecule
after final product cleavage from the resin, (iii) O-glycosyl
trichloroacetimidates [for chain extension, branching or ter-
mination as powerful glycosyl donors, which can be readily
activated by catalytic amounts of (Lewis) acid], and (iv)
benzoic acid residues on the Merrifield resin for the linkage
of the hydroxymethylbenzyl spacer.
Application of this methodology to the synthesis of
Lewis X (Lex) and Lewis A (Lea) oligosaccharides and gan-
gliosides (Scheme 1, B–D) requires 3-O,4-O-branching at
the N-acetylglucosamine and galactose residues, respec-
tively. However, cleavage of one of the temporary ester pro-
tecting groups may be accompanied by migration of the
remaining temporary ester protecting group to the liberated
vicinal hydroxy group. A detailed investigation of the or-
thogonality, including the desirable regioselectivity
of temporary ester protecting groups under SPOS con-
ditions, was therefore undertaken in order to identify a suit-
Oligosaccharides play important roles in various bio-
logical processes, so general interest in these compounds,
particularly as constituents of glycoconjugates, has greatly
increased in recent years.[1–4] As a consequence, oligosac-
charide synthesis has become an important issue.[5–10] In
addition, successful solid-phase oligosaccharide syntheses
(SPOS) have been developed,[11,12] complemented by meth-
ods to avoid undesired byproducts in the synthesis of the
target molecules.[13–16] With our ester-based SPOS design[17]
very good results have been obtained.[6,17,18] To cope with
complex oligosaccharide synthesis, besides the linker-spacer
system corresponding to a temporary protecting group that
is orthogonal to all other protecting groups, three types of
building blocks are required: for controlled chain extension,
branching and termination. A study on the orthogonality
of temporarily ester-group-protected diols required for the
synthesis of branched oligosaccharides, and for diols in ge-
neral, is reported.
[‡] Fmoc- and Alloc-O-protection leads to diesters of carbonic
acid. Hence, the use of the term “ester groups” for O-acylated
and O-alkoxycarbonylated hydroxy groups seems to be reason-
able.
[a] Universität Konstanz, Fachbereich Chemie,
Fach 725, 78457 Konstanz, Germany
Fax: +49-7531-883135
E-mail: richard.schmidt@uni-konstanz.de
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.200900627.
5002
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 5002–5011

Temporary Carbohydrate Diol Protection with Ester Groups
Scheme 1. Typical branched oligosaccharides.
Scheme 2. Synthesis of glucosamine derivatives with temporary
protection at 3-O and 4-O. Reagents and conditions: (a) Fmoc-Cl,
pyridine, DMAP, 0 °C; (b) PA-Cl, pyridine, 0 °C; (c) Lev-OH,
DCC, DMAP, CH2Cl2, room temp.; (d) Alloc-Cl, CH2Cl2/pyridine,
–10 °C; (e) Et3SiH, trifluoroacetic anhydride (TFAA), trifluoro-
acetic acid (TFA), 0 °C Ǟ room temp.
able system for the precise synthesis of branched oligosac-
charides. Because N-acetylglucosamine is frequently found
at the branching points of oligosaccharides (see Lewis anti-
gens in Scheme 1), glucosamine derivatives with temporary
ester protecting groups at 3-O and 4-O were selected for
these studies.
To this end, glucosamine was transformed into the 3-O- compounds 4ab, 4ac and 4ad. Correspondingly, introduc-
unprotected derivative 1 (Scheme 2) according to reported tion of the Fmoc group at 4-O in 3b, 3c and 3d led to 4ba,
procedures.[19] As temporary ester protecting groups at 3- 4ca and 4da. In this way, 4ab and 4ba had Fmoc/PA protec-
O, 9-fluorenylmethoxycarbonyl (Fmoc), phenoxyacetyl tion at 3-O and 4-O, 4ac and 4ca had Fmoc/Lev protection,
(PA), levulinoyl (Lev) and allyloxycarbonyl (Alloc) were in- and 4ad and 4da had Fmoc/Alloc protection. The Fmoc/
troduced, affording compounds 2a, 2b, 2c[20] and 2d. Selec- PA pair (4ab/4ba) and the Fmoc/Lev pair (4ac/4ca) were
tive cleavage of these groups can be performed as follows: selected because these groups had previously been em-
Fmoc is cleaved with triethylamine, PA is removed with so- ployed in SPOS for the synthesis of other branched oligo-
dium methoxide in methanol, Lev is removed with hydraz- saccharides.[17,18,22] The particularly mild cleavage condi-
inium acetate, and Alloc is cleaved with Pd0 in the presence tions for the Fmoc and Alloc groups, which should be tot-
of a nucleophile. PA cleavage conditions will not affect O- ally orthogonal, were the reason for investigating the 4ad/
benzoyl groups, but they will affect O-Fmoc, O-Lev and O- 4da pair.
Alloc groups, so the presence of an O-PA group limits the
The conditions employed for the cleavage of the Fmoc,
cleavage sequence.
PA and Lev groups followed reported work on SPOS on
Reductive opening of the benzylidene acetal groups in Merrifield resins.[11,17,18] Firstly, Fmoc cleavage with trieth-
compounds 2a–2d with triethylsilane in the presence of tri- ylamine (100 equiv.) in dichloromethane as solvent was in-
fluoroacetic anhydride[21] afforded the 4-O-unprotected 6- vestigated in the presence of the 4-O-PA group in 4ab
O-benzylated derivatives 3a, 3b, 3c[20] and 3d, which were (Scheme 3). However, beside the desired 3-O-unprotected
employed for the generation of three pairs with regioisom- 5b, PA migration to 3-O, affording compound 3b (5b/3b =
eric 3-O,4-O-protection. In previous work, the Fmoc group 40:60), was also observed. Similar results were obtained
had turned out to be ideally suited as a temporary protect- when starting from 4ba (5b/3b = 60:40) and also when pure
ing group in SPOS, so in 3a this group was complemented 3b was investigated: under these reaction conditions, 5b/3b
by the PA, Lev and Alloc groups at 4-O, thus leading to were again obtained in a 40:60 ratio. Not unexpectedly, se-
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S. D. Markad, R. R. Schmidt
FULL PAPER
lective cleavage of the PA group in 4ab or 4ba with NaOMe
in MeOH (0.5 equiv.) was also not possible: both groups
were removed to afford the 3-O,4-O-unprotected compound
6. Hence, in contrast with observations made for Fmoc and
PA in remote positions,[17] these groups cannot be employed
as temporary protecting groups in vicinal positions.
O-Lev-protected compound 3c, respectively, both practi-
cally exclusively (Scheme 4). The other way around, initial
Lev cleavage in 4ac and 4ca with hydrazinium acetate also
selectively afforded the desired 3-O-Fmoc protected 3a or
the 4-O-Fmoc protected 5a, respectively. Previous work by
Boons et al.[22] could thus be confirmed. Hence, under these
cleavage conditions, Fmoc and Lev are orthogonal protect-
ing groups for vicinal hydroxy groups. Some Lev migration
was observed when Fmoc cleavage was performed with pi-
peridine (100 equiv.), however, with compounds 5c/3c being
obtained in a 82:18 ratio when starting from 4ac and in a
7:93 ratio when starting from 4ca. Previous SPOS with a
building block structurally closely related to 4ac[18] might
hence have led to some regioisomeric glycosylation product
under the applied piperidine cleavage conditions.
In our SPOS experiments, complete removal of hydrazin-
ium acetate from the resin before the next glycosylation step
had turned out to be difficult,[23] so the Fmoc/Alloc pair in
4ad/4da was investigated for temporary protection of the
vicinal 3-O,4-O-hydroxy groups. Gratifyingly, treatment of
4ad and 4da with triethylamine in dichloromethane led
practically exclusively to 3-O-unprotected 5d or to 4-O-un-
protected 3d, respectively (Scheme 5). Similarly, treatment
Scheme 3. Cleavage of the temporary Fmoc and PA protecting
groups in 4ab and 4ba.
Investigation of Fmoc cleavage with triethylamine in the
presence of the Lev group in 4ac/4ca under SPOS condi-
tions afforded the desired 4-O-Lev-protected 5c and the 3- of 4ad and 4da with tetrakis(triphenylphosphane)palladium
Scheme 4. Cleavage of the temporary Fmoc and Lev protecting groups in 4ac and 4ca.
Scheme 5. Cleavage of the temporary Fmoc and Alloc protecting groups in 4ad and 4da.
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Eur. J. Org. Chem. 2009, 5002–5011

Temporary Carbohydrate Diol Protection with Ester Groups
(Pd0) as catalyst and excess dimedone as nucleophile in conditions that limit its use for the temporary protection
THF[24] exclusively furnished 4-O-unprotected 3a and 3-O- of vicinal hydroxy groups in SPOS. Excellent results were
unprotected 5a, respectively. When the quite basic sodium obtained for the Fmoc/Alloc pair (4ad/4da), which could be
p-toluenesulfinate was employed as nucleophile in this reac- orthogonally cleaved under mild conditions independent of
tion, however (starting from 4da, for instance), 3a and 5a the position and the sequence. Not surprisingly, the same
were obtained in a 45:55 ratio, pointing to Fmoc migration results were obtained for Fmoc cleavage in combination
under these conditions. Preliminary SPOS studies showed with the ether-linked Nap group (4ea). Regiocontrolled syn-
that the Fmoc/Alloc pair is highly useful for temporary pro- thesis of branched oligosaccharides is now being carried out
tection in order to access branched oligosaccharides.[25]
To provide further options in orthogonal protection of
vicinal hydroxy groups, a combination of the Fmoc group
with the 2-naphthylmethyl (Nap) group ether-linked to the
3-O-position was also investigated (Scheme 6). To this end,
the 3-O-Nap-protected compound 2e was prepared from 1
and O-naphthylmethyl trichloroacetimidate[26] and, after re-
ductive benzylidene cleavage (Ǟ 3e) and 4-O-Fmoc protec-
tion, afforded the desired starting material 4ea. Gratify-
ingly, selective removal of the two groups – either Fmoc
with triethylamine to afford 4-O-unprotected 3e exclusively
or Nap with DDQ to afford 5a exclusively – offered a fur-
ther useful alternative for temporary protection of vicinal
hydroxy groups.
with these systems.
Experimental Section
General: Solvents were purified by standard procedures. NMR
spectra were recorded at 22 °C with a Bruker 400 spectrometer; tet-
ramethylsilane (TMS) or the resonance of the undeuterated solvent
were used as internal standards (solvent CDCl3, δ = 7.24 ppm).
Mass spectra were recorded with a Bruker ESI-MS mass spectrom-
eter. Thin-layer chromatography was performed on Merck silica gel
(60 F254) plastic plates; compounds were visualized by treatment
with a solution of (NH4)6Mo7O24·4H2O (20 g) and Ce(SO4)2 (0.4 g)
in sulfuric acid (10%, 400 mL) and then by heating to 120 °C.
Flash chromatography was performed on MN Silica gel 60 (230–
400 mesh) at a pressure of 0.2 bar. Optical rotations were measured
at 22 °C with a Büchi Polar-Monitor using sodium D line light.
A. General Procedure for 9-Fluorenylmethoxycarbonylation:
FmocCl (1.2 mmol), followed by DMAP (0.01 mmol), were added
at 0 °C to a solution of the compound (1 mmol) in dry pyridine
(10 mL), and the resulting reaction mixture was allowed to warm
to room temperature and stirred for 2–4 h. The reaction mixture
was quenched by addition of excess methanol (1 mL) and concen-
trated under reduced pressure to give a residue.
B. General Procedure for Phenoxyacetylation: Phenoxyacetyl chlo-
ride (PACl, 1.2 mmol) was added dropwise at 0 °C to a solution of
the compound (1 mmol) in dry pyridine (10 mL), and the resulting
reaction mixture was stirred for 30 min at the same temperature.
The reaction mixture was quenched by addition of excess methanol
(1 mL) and concentrated under reduced pressure to give a residue.
C. General Procedure for the Reductive Opening of the 4,6-O-
Benzylidene Ring: Triethylsilane (5.0 mmol), followed by trifluoro-
acetic anhydride (3.0 mmol), were added at 0 °C to a solution of
the compound (1 mmol) in dry CH2Cl2 (10 mL). TFA (5.0 mmol)
was added dropwise over a period of 10 min, and the reaction mix-
ture was allowed to warm to room temperature and stirred for 2–
4 h. The reaction mixture was quenched by dropwise addition of
cold saturated NaHCO3 and extracted with CH2Cl2 (15 mL ϫ3).
The organic layer was washed with water (10 mL ϫ3), dried with
anhydrous MgSO4 and concentrated under reduced pressure to give
a residue.
Scheme 6. Synthesis of the glucosamine derivative 4ea and cleavage
of the temporary Fmoc and Nap protecting groups.
D. General Procedure for Fmoc Removal: Triethylamine (10 mmol)
or piperidine (10 or 17.5 mmol) was added to a solution of the
compound (0.1 mmol) in CH2Cl2 (10 mL), and the resulting reac-
tion mixture was stirred at room temp. for 40 min to 3 h. Volatiles
were removed under reduced pressure, and the residue was purified
by column chromatography.
Conclusions
The compound pairs 4ab/4ba, 4ac/4ca and 4ad/4da, with
temporary ester protecting groups at vicinal 3-O and 4-O
for the regiocontrolled synthesis of branched oligosaccha-
rides together with tert-butyldimethylsilyl (TBS) groups at
their anomeric hydroxy groups for eventual transformation
of these intermediates into glycosyl donors, were investi-
gated under SPOS cleavage conditions. The Fmoc/PA pair
(4ab/4ba) did not comply with the stability requirements,
tert-Butyldimethylsilyl 4,6-O-Benzylidene-2-deoxy-2-dimethylmale-
imido-3-O-(9-fluorenylmethoxycarbonyl)-β-D-glucopyranoside (2a):
The residue obtained from 1 after General Procedure A was puri-
fied by column chromatography (petroleum ether/ethyl acetate, 9:1)
to give 2a (7.0 g, 96%) as a colourless foam. Rf = 0.45 (petroleum
1
and the Fmoc/Lev pair (4ac/4ca) also required cleavage ether/ethyl acetate, 8:2). [α]2D2 = +15.3 (c = 1.0, CHCl3). H NMR
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S. D. Markad, R. R. Schmidt
FULL PAPER
(400 MHz, CDCl3): δ = 7.74 (d, J = 7.7 Hz, 2 H, Ar-H), 7.54 (d,
68.6 (C-6/OCH2CH=), 66.2 (C-5), 57.2 (C-2), 25.4 [SiC(CH3)3],
J = 7.5 Hz, 1 H, Ar-H), 7.46–7.52 (m, 3 H, Ar-H), 7.31–7.42 (m, 17.7 [SiC(CH3)3], 8.8 (DMM-CH3), –4.1, –5.5 (2ϫ SiCH3) ppm.
5 H, Ar-H), 7.29 (dt, J = 7.2, 1.0 Hz, 1 H, Ar-H), 7.22 (dt, J = 7.3,
ESI-HRMS (positive mode): calcd. for [C29H39NO9Si+Na]+
1.0 Hz, 1 H, Ar-H), 5.61 (dd, J = 10.4, 9.6 Hz, 1 H, 3-H), 5.44 (s, 596.2286; found 596.2273. C29H39NO9Si (573.71): calcd. C 60.71,
1 H, PhCH), 5.38 (d, J = 8.0 Hz, 1 H, 1-H), 4.25 (dd, J = 10.8,
5.1 Hz, 1 H, 6-Hb), 4.12–4.15 (m, 2 H, Fmoc-CH2), 4.09 (dd, J =
10.5, 8.0 Hz, 1 H, 2-H), 4.03 (t, J = 7.6 Hz, 1 H, Fmoc-CH), 3.75
(dd, J = 10.3, 3.6 Hz, 1 H, 4-H), 3.72 (dd, J = 10.2, 4.0 Hz, 1 H,
6-Ha), 3.61 (ddd, J = 14.3, 9.6, 4.5 Hz, 1 H, 5-H), 1.74 (s, 6 H,
DMM-CH3), 0.70 [s, 9 H, SiC(CH3)3], 0.00 (s, 3 H, SiCH3), –0.09
(s, 3 H, SiCH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 154.5
(CO), 143.3, 143.2, 141.2, 141.1, 137.4, 137.0, 129.2, 128.3, 127.9,
127.8, 127.4, 127.3, 126.4, 125.3, 125.2, 120.0, (Ar-C), 101.7
(PhCH), 93.9 (C-1), 79.5 (C-4), 74.4, 73.7 (C-3), 70.3 (Fmoc-CH2),
68.7 (C-6), 66.2 (C-5), 57.3 (C-2), 46.5 (Fmoc-CH), 25.4
[C(CH3)3], 17.6 [C(CH3)3], 8.7 (DMM-CH3), –4.1, –5.5 (2ϫ
SiCH3) ppm. ESI-HRMS (positive mode): calcd. for
[C40H45NO9Si+Na]+ 734.2756; found 734.2739. C40H45NO9Si
(711.87): calcd. C 67.49, H 6.37, N 1.97; found C 67.26, H 6.12, N
1.87.
H 6.85, N 2.44; found C 60.61, H 7.05, N 2.34.
tert-Butyldimethylsilyl 6-O-Benzyl-2-deoxy-2-dimethylmaleimido-3-
O-(9-fluorenylmethoxycarbonyl)-β-D-glucopyranoside (3a): The resi-
due obtained from 2a after General Procedure C was purified by
column chromatography (petroleum ether/ethyl acetate, 8:2) to give
3a (6.40 g, 91%) as a foam. Rf = 0.41 (petroleum ether/ethyl ace-
tate, 7:3). [α]2D2 = +36.3 (c = 1.0, CHCl3). 1H NMR (400 MHz,
CDCl3): δ = 7.64 (d, J = 7.1 Hz, 2 H, Ar-H), 7.46 (d, J = 7.1 Hz,
1 H, Ar-H), 7.40 (d, J = 7.5 Hz, 1 H, Ar-H), 7.32–7.14 (m, 9 H,
Ar-H), 5.44 (dd, J = 11.1, 9.1 Hz, 1 H, 3-H), 5.32 (d, J = 8.1 Hz,
1 H, 1-H), 4.51 (ABq, J = 12.4 Hz, 2 H, OCH2Ph), 4.22–4.12 (m,
2 H, Fmoc-CH2), 4.05 (t, J = 7.6 Hz, 1 H, Fmoc-CH), 3.99 (dd, J
= 10.8, 8.0 Hz, 1 H, 2-H), 3.75 (t, J = 9.3 Hz, 1 H, 4-H), 3.72 (d,
J = 4.5 Hz, 2 H, 6a,b-H), 3.65 (dt, J = 9.9, 4.5 Hz, 1 H, 5-H), 3.13–
2.89 (br. s, 1 H, OH), 1.74 (s, 6 H, 2ϫ CH3), 0.69 [s, 9 H, SiC-
(CH3)3], 0.00 (s, 3 H, SiCH3), –0.10 (s, 3 H, SiCH3) ppm. 13C NMR
(101 MHz, CDCl3): δ = 155.5 (CO), 143.4, 143.2, 141.3, 141.3,
137.9, 137.5, 128.6, 128.4, 128.0, 128.0, 127.9, 127.8, 127.4, 125.4,
125.4, 120.1 (Ar-C), 93.3 (C-1), 77.3 (C-3), 74.3 (C-5), 73.8
(OCH2Ph), 71.7 (C-4), 70.5, 70.4 (C-6, Fmoc-CH2), 56.6 (C-2), 46.6
(Fmoc-CH), 25.5 [SiC(CH3)3], 17.7 [SiC(CH3)3], 8.8 (DMM-CH3),
–4.0, –5.5 (2ϫ SiCH3) ppm. ESI-HRMS (positive mode): calcd.
for [C40H47NO9Si+Na]+ 736.2912; found 736.2896. C40H47NO9Si
(713.89): calcd. C 67.30, H 6.64, N 1.96; found C 66.39, H 7.00, N
1.69.
tert-Butyldimethylsilyl 4,6-O-Benzylidene-2-deoxy-2-dimethylmale-
imido-3-O-phenoxyacetyl-β-D-glucopyranoside (2b): The residue ob-
tained from 1 after General Procedure B was purified by column
chromatography (petroleum ether/ethyl acetate, 9:1) to give 2b
(5.70 g, 93%) as a white foam. Rf = 0.55 (petroleum ether/ethyl
acetate, 8:2). [α]2D2 = –13.9 (c = 1.0, CHCl3). H NMR (400 MHz,
1
CDCl3): δ = 7.42–7.35 (m, 2 H, Ar-H), 7.33–7.28 (m, 3 H, Ar-H),
7.05 (t, J = 7.6 Hz, 2 H, Ar-H), 6.84 (t, J = 7.3 Hz, 1 H, Ar-H),
6.70 (d, J = 8.4 Hz, 2 H, Ar-H), 5.83 (dd, J = 9.6 Hz, 1 H, 3-H),
5.41 (s, 1 H, CHPh), 5.40 (d, J = 8.1 Hz, 1 H, 1-H), 4.48 (ABq, J
= 17.0 Hz, 2 H, –CH2OPh), 4.28 (dd, J = 10.6, 4.5 Hz, 1 H, 6-Hb),
4.00 (dd, J = 10.3, 8.1 Hz, 1 H, 2-H), 3.76 (t, J = 10.0 Hz, 1 H, 6-
Ha), 3.71–3.59 (m, 2 H, 4-H/5-H), 1.85 (s, 6 H, DMM-CH3), 0.71
[s, 9 H, –SiC(CH3)3], 0.00 (s, 3 H, SiCH3), –0.09 (s, 3 H, SiCH3)
ppm. 13C NMR (101 MHz, CDCl3): δ = 168.5 (CO), 157.8 (OCO),
137.1, 129.7, 129.4, 128.5, 126.5, 121.8, 114.7 (Ar-C), 101.9
(PhCH), 94.0 (C-1), 79.6 (C-4), 70.9 (C-3), 68.9 (C-6), 66.3 (C-5),
65.0 (PhOCH2), 57.3 (C-2), 25.5 [SiC(CH3)3], 17.8 [SiC(CH3)3], 8.9
(DMM-CH3), –4.0, –5.5 (2ϫ SiCH3) ppm. ESI-HRMS (positive
mode): calcd. for [C33H41NO9Si+Na]+ 646.2443; found 746.2404.
tert-Butyldimethylsilyl 6-O-Benzyl-2-deoxy-2-dimethylmaleimido-3-
O-phenoxyacetyl-β-D-glucopyranoside (3b): The residue obtained
from 2b after General Procedure C was purified by column
chromatography (petroleum ether/ethyl acetate, 9:1) to give 3b
(2.45 g, 85%) as a viscous liquid. Rf = 0.66 (petroleum ether/ethyl
1
acetate, 7:3). [α]2D2 = –3.75 (c = 0.8, CHCl3). H NMR (400 MHz,
CDCl3): δ = 7.29–7.14 (m, 5 H, Ar-H), 7.10 (t, J = 8.0 Hz, 2 H,
Ar-H), 6.82 (t, J = 7.3 Hz, 1 H, Ar-H), 6.68 (d, J = 8.0 Hz, 2 H,
Ar-H), 5.67 (dd, J = 10.8, 8.3 Hz, 1 H, 3-H), 5.35 (d, J = 8.0 Hz,
1 H, 1-H), 4.49 (s, 2 H, OCH2Ph) 4.43 (ABq, J = 16.2 Hz, 2 H,
PhOCH2), 3.89 (dd, J = 10.9, 8.0 Hz, 1 H, 2-H), 3.75–3.52 (m, 4
H, 4-H/5-H/6-Hab), 3.35–3.01 (br. s, 1 H, OH), 1.75 (s, 6 H, DMM-
CH3), 0.68 [s, 9 H, –SiC(CH3)3], –0.00 (s, 3 H, SiCH3), –0.10 (s, 3
H, SiCH3) ppm. 13C NMR (101 MHz, CDCl3): δ = 169.5 (CO),
157.7 (CO), 138.1, 129.6, 128.5, 127.7, 127.6, 121.7, 114.6 (Ar-C),
93.1 (C-1), 74.8 (C-4/C-5), 74.4 (C-3), 73.6 (OCH2Ph), 71.0 (C-4/
C-5), 70.0 (C-6), 64.9 (PhOCH2), 56.6 (C-2), 25.4 [SiC(CH3)3], 17.6
[SiC(CH3)3], 8.7 (DMM-CH3), –4.1, –5.6 (2ϫ SiCH3) ppm. ESI-
HRMS (positive mode): calcd. for [C33H43NO9Si+Na]+ 648.2599;
found 648.2590.
tert-Butyldimethylsilyl 3-O-Allyloxycarbonyl-4,6-O-benzylidene-2-
deoxy-2-dimethylmaleimido-β-D-glucopyranoside
(2d): AllocCl
(1.06 mL, 12.44 mmol) was added at –10 °C to a solution of com-
pound 1 (1.74 g, 3.55 mmol) in CH2Cl2/pyridene (3:2, 35 mL) over
a period of 10 min, and the resulting reaction mixture was stirred
at the same temperature for 1 h. The reaction mixture was
quenched by addition of excess MeOH (5 mL) and concentrated
under reduced pressure. The residue was purified by column
chromatography (petroleum ether/ethyl acetate, 9:1) to give 2d
(1.94 g, 95%) as a syrup. Rf = 0.60 (petroleum ether/ethyl acetate,
1
7:3). [α]2D2 = –36.5 (c = 1.0, CHCl3). H NMR (400 MHz, CDCl3):
tert-Butyldimethylsilyl 3-O-Allyloxycarbonyl-6-O-benzyl-2-deoxy-2-
δ = 7.42–7.34 (m, 2 H, Ar-H) 7.31–7.23 (m, 3 H, Ar-H), 5.77–5.66
(m, 1 H, –CH=CH2), 5.56 (dd, J = 10.6, 9.2 Hz, 1 H, 3-H), 5.44
(s, 1 H, CHPh), 5.36 (d, J = 7.8 Hz, 1 H, 1-H), 5.15 (dd, J = 17.2,
1.3 Hz, 1 H, –OCH2CH=CH2), 5.07 (dd, J = 10.9, 1.3 Hz, 1 H,
dimethylmaleimido-β-D-glucopyranoside (3d): The residue obtained
from 2d after General Procedure C was purified by column
chromatography (petroleum ether/ethyl acetate, 8:2) to give 3d
(1.7 g, 88%) as a viscous syrup. Rf = 0.43 (petroleum ether/ethyl
–OCH2CH=CH2), 4.48–4.37 (m, 2 H, OCH2CH=CH2), 4.26 (dd, acetate, 7:3). [α]2D2 = –6.0 (c = 1.0, CHCl3). 1H NMR (400 MHz,
J = 10.5, 5.1 Hz, 1 H, 6-Ha), 4.02 (dd, J = 10.3, 7.8 Hz, 1 H, 2-
H), 3.74 (t, J = 10.0 Hz, 1 H, 6-Ha), 3.69 (t, J = 9.3 Hz, 1 H, 4-
CDCl3): δ = 7.29–7.15 (m, 5 H, Ar-H) 5.79–5.67 (m, 1 H,
CH=CH2), 5.37 (dd, J = 11.1, 8.3 Hz, 1 H, 3-H), 5.31 (d, J =
H), 3.60 (ddd, J = 9.5, 5.4, 4.6 Hz, 1 H, 5-H), 1.88 (s, 6 H, DMM- 8.1 Hz, 1 H, 1-H), 5.17 (dd, J = 17.3, 1.1 Hz, 1 H, –OCH2CH=),
CH3), 0.71 [s, 9 H, Si(CH3)3], 0.00 (s, 3 H, SiCH3), –0.08 (s, 3 H,
SiCH3) ppm. 13C NMR (101 MHz, CDCl3): δ = 154.3 (OCO),
137.1, 131.4 (OCH2CH=CH2), 129.2, 128.3, 126.4 (Ar-C), 118.6
5.10 (dd, J = 10.5, 1.1 Hz, 1 H, –OCH2CH=), 4.52 (ABq, J =
12.3 Hz, 2 H, OCH2Ph), 4.48–4.38 (m, 2 H, OCH2CH=), 3.92 (dd,
J = 11.0, 8.1 Hz, 1 H, 2-H), 3.74–3.60 (m, 4 H, 4-H/5-H/6-Ha,b),
(CH=CH2), 101.7 (CHPh), 93.9 (C-1), 79.5 (C-4), 73.6 (C-3), 68.8, 3.21–2.83 (br. s, 1 H, OH), 1.84 (s, 6 H, DMM-CH3), 0.69 [s, 9 H,
5006
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© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 5002–5011

Temporary Carbohydrate Diol Protection with Ester Groups
SiC(CH3)3], 0.00 (s, 3 H, SiCH3), –0.09 (s, 3 H, SiCH3) ppm. 13C
tert-Butyldimethylsilyl 4-O-Allyloxycarbonyl-6-O-benzyl-2-deoxy-2-
δ = 155.2 (OCO), 138.0, 131.4 dimethylmaleimido-3-O-(9-fluorenylmethoxycarbonyl)-β-D-glucopyr-
NMR (101 MHz, CDCl3):
(CH=CH2), 128.5, 127.8, 127.7 (Ar-C), 118.8 (CH=CH2), 93.2 (C- anoside (4ad): (Alloc)2O (116 µL, 0.70 mmol) was added to a solu-
1), 77.2 (C-3), 74.4 (C-5), 73.7 (OCH2Ph), 71.4 (C-4), 70.2 (C-6), tion of compound 3a (0.05 g, 0.07 mmol) in CH2Cl2/pyridine (2:1,
68.8 (-OCH2CH=), 56.5 (C-2), 25.4 [C(CH3)3], 17.7 [C(CH3)3], 8.7 3 mL), and the resulting reaction mixture was stirred at room tem-
(DMM-CH3), –4.1, –5.5 (2ϫ SiCH3) ppm. ESI-HRMS (positive
mode): calcd. for [C29H41NO9Si+Na]+ 598.2443; found 598.2468.
C29H41NO9Si (575.72): calcd. C 60.50, H 7.18, N 2.43; found C
59.79, H 7.34, N 2.18.
perature for 16 h. The reaction mixture was quenched with excess
methanol (1 mL) and concentrated under reduced pressure to give
a viscous mass. Column purification afforded 4ad (0.028 g, 50%)
as a foam, together with the starting material 3a (0.013 g, 26%). Rf
= 0.45 (petroleum ether/ethyl acetate, 8:2). [α]2D2 = +34.0 (c = 1.0,
CHCl3). 1H NMR (400 MHz, CDCl3): δ = 7.76–7.69 (d, J =
7.4 Hz, 2 H, Ar-H), 7.56–7.48 (t, J = 8.4 Hz, 2 H, Ar-H), 7.38 (t,
J = 7.4 Hz, 2 H, Ar-H), 7.35–7.23 (m, 7 H, Ar-H), 5.78–5.67 (m,
1 H, CH2=CH–CH2), 5.65 (dd, J = 10.8, 9.1 Hz, 1 H, 3-H), 5.38
(d, J = 8.0 Hz, 1 H, 1-H), 5.17 (dd, J = 17.2, 1.4 Hz, 1 H, OCHH–
CH=), 5.09 (dd, J = 10.4, 1.2 Hz, 1 H, OCHH–CH=), 5.06 (dd, J
= 9.8, 9.4 Hz, 1 H, 4-H), 4.57 (ABq, J = 12.1 Hz, 2 H, OCH2Ph),
4.45 (d, J = 5.7 Hz, 2 H, OCH2–CH=), 4.28–4.19 (m, 2 H, Fmoc-
CH2), 4.18 (J = 10.8, 8.0 Hz, 1 H, 2-H), 4.13 (t, J = 7.3 Hz, 1 H,
Fmoc-CH), 3.86 (dt, J = 10.1, 4.4 Hz, 1 H, 5-H), 3.67 (d, J =
4.3 Hz, 2 H, 6-Hab), 1.84 (br. s, 6 H, DMM-CH3), 0.77 [s, 9 H,
SiC(CH3)3], 0.09 (s, 3 H, SiCH3), –0.01 (s, 3 H, SiCH3) ppm. 13C
NMR (101 MHz, CDCl3): δ = 154.6, 154.2 (2 ϫ OCO), 143.5,
143.3, 141.3, 138.1, 137.6, 131.3 (HC=CH2), 128.5, 128.1, 128.0,
127.8, 127.7, 127.5, 127.5, 125.5, 125.5, 120.1 (Ar-C), 119.1
(HC=CH2), 93.4 (C-1), 74.8 (C-3), 74.3 (C-4), 73.7 (OCH2Ph), 73.1
(C-5), 70.6 (Fmoc-CH2), 69.4 (C-6), 69.1 (OCH2–CH=CH2), 56.7
(C-2), 46.6 (Fmoc-CH), 25.5 [SiC(CH3)3], 17.8 [SiC(CH3)3], 8.8
(DMM-CH3), –4.0, –5.4 (2 ϫ SiCH3) ppm. ESI-MS (positive
mode): calcd. for [C44H51NO11Si+Na]+ 820.3124; found 820.3115.
tert-Butyldimethylsilyl 6-O-Benzyl-2-deoxy-2-dimethylmaleimido-3-
O-(9-fluorenylmethoxycarbonyl)-4-O-phenoxyacetyl-β-D-glucopyr-
anoside (4ab): The residue obtained from 3a after General Pro-
cedure B was purified by column chromatography (petroleum
ether/ethyl acetate, 9:1) to give 4ab (0.219 g, 92%) as a foam. Rf =
0.52 (petroleum ether/ethyl acetate, 8:2). [α]2D2 = +32.3 (c = 1.0,
1
CHCl3). H NMR (400 MHz, CDCl3): δ = 7.59 (d, J = 3.6 Hz, 1
H, Ar-H), 7.58 (d, J = 3.4 Hz, 1 H, Ar-H), 7.40 (d, J = 7.6 Hz, 1
H, Ar-H), 7.35 (d, J = 7.5 Hz, 1 H, Ar-H), 7.27–7.08 (9 H, Ar-H),
7.08–7.02 (m, 2 H, Ar-H), 6.82–6.76 (m, 1 H, Ar-H), 6.69–6.63 (m,
2 H, Ar-H), 5.54 (dd, J = 10.9, 9.1 Hz, 1 H, 3-H), 5.29 (d, J =
8.0 Hz, 1 H, 1-H), 5.24 (dd, J = 9.8, 9.3 Hz, 1 H, 4-H), 4.38 (ABq,
J = 12.0 Hz, 2 H, OCH2Ph), 4.30 (ABq, J = 16.1 Hz, 2 H,
PhOCH2), 4.10 (dd, J = 9.3, 8.0 Hz, 1 H, 2-H), 4.08–4.02 (m, 2 H,
Fmoc-CH2), 3.98 (t, J = 7.7 Hz, 1 H, Fmoc-CH), 3.71 (dt, J = 9.9,
4.2 Hz, 1 H, 5-H), 3.46 (m, 2 H, 6-Ha,b), 1.72 (s, 6 H, DMM-
CH3), 0.68 [s, 9 H, SiC(CH3)3], –0.00 (s, 3 H, SiCH3), –0.10 (s, 3
H, SiCH3) ppm. 13C NMR (101 MHz, CDCl3): δ = 171.4, 167.9
(2ϫ CO), 157.6 (OCO), 154.5, 143.2, 143.1, 141.2, 141.2, 137.8,
137.5, 129.6, 128.4, 127.9, 127.9, 127.8, 127.8, 127.3, 125.3, 125.2,
121.8, 120.0, 114.6 (Ar-C), 93.3 (C-1), 74.6 (C-3), 73.6 (OCH2Ph), tert-Butyldimethylsilyl 6-O-Benzyl-2-deoxy-2-dimethylmaleimido-4-
72.7 (C-5), 71.1 (C-4), 70.5 (Fmoc-CH2), 69.3 (C-6), 65.0 O-(9-fluorenylmethoxycarbonyl)-3-O-phenoxyacetyl-β- -glucopyr-
D
(PhOCH2), 56.6 (C-2), 46.4 (Fmoc-CH), 25.4 [SiC(CH3)3], 17.6 anoside (4ba): The residue obtained from 3b after General Pro-
[SiC(CH3)3], 8.7 (DMM-CH3), –4.1 (SiCH3), –5.5 (SiCH3) ppm. cedure A was purified by column chromatography (petroleum
ESI-HRMS (positive mode): calcd. for [C48H53NO11Si+Na]+
870.3280; found 870.3256.
ether/ethyl acetate, 9:1) to give 4ba (5.10 g, 85%) as a white foam.
Rf = 0.45 (petroleum ether/ethyl acetate, 8:2). [α]2D2 = +17.0 (c =
0.8, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 7.65 (t, J = 6.7 Hz,
2 H, Ar-H), 7.46–7.39 (m, 2 H, Ar-H), 7.33–7.09 (m, 9 H, Ar-H),
7.05 (t, J = 7.9 Hz, 2 H, Ar-H), 6.79 (t, J = 7.3 Hz, 1 H, Ar-H),
6.64 (d, J = 8.3 Hz, 2 H, Ar-H), 5.79 (dd, J = 9.5, 9.1 Hz, 1 H, 3-
H), 5.33 (d, J = 8.0 Hz, 1 H, 1-H), 4.91 (t, J = 9.5 Hz, 1 H, 4-H),
4.46 (ABq, J = 12.1 Hz, 2 H, OCH2Ph), 4.35 (ABq, J = 16.8 Hz,
2 H, PhOCH2), 4.22–4.11 (m, 2 H, Fmoc-CH2), 4.04 (t, J = 7.8 Hz,
1 H, Fmoc-CH), 3.98 (J = 10.8, 8.0 Hz, 1 H, 2-H), 3.80 (dt, J =
10.1, 4.0 Hz, 1 H, 5-H), 3.56 (d, J = 4.0 Hz, 2 H, 6-Hab), 1.81 (s,
6 H, DMM-CH3), 0.68 [s, 9 H, –SiC(CH3)3], –0.00 (s, 3 H, –SiCH3),
–0.10 (s, 3 H, –SiCH3) ppm. 13C NMR (101 MHz, CDCl3): δ =
171.5 (CO), 168.5 (CO), 157.7 (OCO), 154.4, 143.3, 143.3, 141.5,
141.4, 138.1, 129.6, 128.5, 128.1, 127.8, 127.7, 127.5, 127.4, 125.3,
121.9, 120.3, 120.2, 114.7 (Ar-C), 93.4 (C-1), 74.2 (C-4), 73.7
(OCH2Ph), 73.1 (C-5), 72.1 (C-3), 70.5 (Fmoc-CH2), 69.3 (C-6),
65.0 (PhOCH2), 56.8 (C-2), 46.7 (Fmoc-CH), 25.5 [SiC(CH3)3],
17.8 [SiC(CH3)3], 8.9 (DMM-CH3), –4.0, –5.4 (2ϫ SiCH3) ppm.
ESI-HRMS (positive mode): calcd. for [C48H53NO11Si+Na]+
870.3280; found 870.3248.
tert-Butyldimethylsilyl 6-O-Benzyl-2-deoxy-2-dimethylmaleimido-3-
O-(9-fluorenylmethoxycarbonyl)-4-O-levulinoyl-β-D-glucopyranoside
(4ac): DCC (0.274 g, 1.33 mmol), followed by a catalytic amount
of DMAP, was added to a solution of compound 3a (0.19 g,
2.04 mmol) and levulinic acid (271 µL, 2.66 mmol) in CH2Cl2
(3 mL) at room temperature, and the mixture was stirred for 1 h.
The milky reaction mixture was concentrated under reduced pres-
sure to give a residue. Column chromatography of the residue af-
forded 4ac (0.17 g, 79%) as a viscous liquid. Rf = 0.43 (petroleum
1
ether/ethyl acetate, 7:3). [α]2D2 = +38.3 (c = 1.0, CHCl3). H NMR
(400 MHz, CDCl3): δ = 7.73 (d, J = 7.5 Hz, 2 H, Ar-H), 7.53 (dd,
J = 7.2, 3.9 Hz, 2 H, Ar-H), 7.31 (m, 9 H, Ar-H), 5.62 (dd, J =
10.5, 9.4 Hz, 1 H, 3-H), 5.38 (d, J = 8.0 Hz, 1 H, 1-H), 5.21 (t, J
= 9.6 Hz, 1 H, 4-H), 4.56 (s, 2 H, OCH2Ph), 4.32–4.12 (m, 4 H,
Fmoc-CH2, 2-H, Fmoc-CH), 3.87–3.77 (m, 1 H, 5-H), 3.62 (m, 2
H, 6-Hab), 2.56 (t, J = 6.4 Hz, 2 H, CH2), 2.40 (t, J = 6.3 Hz, 2
H, CH2), 2.02 (s, 3 H, COCH3), 1.85 (s, 6 H, DMM-CH3), 0.77 [s,
9 H, SiC(CH3)3], 0.10 (s, 3 H, SiCH3), –0.00 (s, 3 H, SiCH3) ppm.
13C NMR (101 MHz, CDCl3): δ = 206.1 (COCH3), 171.5 (CO),
tert-Butyldimethylsilyl 6-O-Benzyl-2-deoxy-2-dimethylmaleimido-4-
154.6 (OCO), 143.5, 143.3, 141.3, 138.2, 137.5, 128.4, 128.0, 127.9, O-(9-fluorenylmethoxycarbonyl)-3-O-levulinoyl-β-
D-glucopyranoside
127.8, 127.7, 127.4, 127.4, 125.5, 120.1 (Ar-C), 93.3 (C-1), 74.8 (C- (4ca): The residue obtained from 3c after General Procedure A was
3), 73.6 (OCH2Ph), 73.4 (C-5), 70.5 (Fmoc-CH2), 70.3 (C-4), 69.4
(C-6), 56.7 (C-2), 46.5 (Fmoc-CH), 37.8 (CH2), 29.7 (COCH3), 28.0
(CH2), 25.5 [SiC(CH3)3], 17.7 [SiC(CH3)3], 8.8 (DMM-CH3), –4.0,
–5.5 (2 ϫ SiCH3) ppm. ESI-HRMS (positive mode): calcd. for
[C45H53NO11Si+Na]+ 834.3280; found 834.3260.
purified by column chromatography (petroleum ether/ethyl acetate,
7:3) to afford 4ca (1.21 g, 88%) as a foam. Rf = 0.35 (petroleum
ether/ethyl acetate, 7:3). [α]2D2 = –2.6 (c = 1.0, CHCl3). 1H NMR
(400 MHz, CDCl3): δ = 7.75 (d, J = 7.6 Hz, 2 H, Ar-H), 7.56 (dd,
J = 10.8, 7.5 Hz, 2 H, Ar-H), 7.39 (dt, J = 7.4, 3.4 Hz, 2 H, Ar-
Eur. J. Org. Chem. 2009, 5002–5011
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5007

S. D. Markad, R. R. Schmidt
FULL PAPER
H), 7.35–7.19 (m, 7 H, Ar-H), 5.83 (dd, J = 10.8, 9.2 Hz, 1 H, 3-
H), 5.41 (d, J = 8.1 Hz, 1 H, 1-H), 4.97 (t, J = 9.6 Hz, 1 H, 4-H),
4.56 (ABq, J = 12.1 Hz, 2 H, OCH2Ph), 4.38 (dd, J = 9.4, 6.9 Hz,
0.69 [s, 9 H, SiC(CH3)3], –0.00 (s, 3 H, SiCH3), –0.09 (s, 3 H,
SiCH3) ppm. 13C NMR (101 MHz, CDCl3): δ = 172.1, 169.0 (2ϫ
CO), 157.7 (OCO), 138.0, 137.3, 129.6, 128.4, 127.8, 127.7, 121.8,
1 H, Fmoc-CHH), 4.23 (dd, J = 9.3, 7.6 Hz, 1 H, Fmoc-CHH), 114.6 (Ar-C), 93.5 (C-1), 74.0 (C-4), 73.4 (OCH2Ph), 72.9 (C-5),
4.19 (t, J = 7.5 Hz, 1 H, Fmoc-CH), 4.03 (dd, J = 10.9, 8.1 Hz, 1
H, 2-H), 3.88 (dt, J = 10.1, 4.0 Hz, 1 H, 5-H), 3.66 (d, J = 4.0 Hz,
69.8 (C-3), 69.4 (C-6), 65.1 (PhOCH2), 59.0 (C-2), 25.4 [SiC-
(CH3)3], 17.6 [SiC(CH3)3], 8.7 (DMM-CH3), –4.1, –5.5 (2ϫ SiCH3)
2 H, 6-Ha,b), 2.60–2.45 (m, 2 H, CH2), 2.41–2.26 (m, 2 H, CH2), ppm. ESI-HRMS (positive mode): calcd. for [C33H43NO9Si+Na]+
1.98 (s, 3 H, COCH3), 1.95 (s, 6 H, DMM-CH3), 0.77 [s, 9 H, 648.2599; found 648.2577.
SiC(CH3)3], 0.09 (s, 3 H, SiCH3), –0.00 (s, 3 H, SiCH3) ppm. 13C
tert-Butyldimethylsilyl 6-O-Benzyl-2-deoxy-2-dimethylmaleimido-3-
NMR (101 MHz, CDCl3): δ = 205.9 (CH3CO), 171.8 (CO), 154.4
O-phenoxyacetyl-β-D-glucopyranoside (3b) and tert-Butyldimethyl-
(OCO), 143.5, 141.4, 141.4, 138.2, 137.5, 128.5, 128.1, 128.1, 127.8,
127.7, 127.4, 125.5, 125.4, 120.2, 120.2 (Ar-C), 93.5 (C-1), 74.3 (C-
4), 73.71 (OCH2Ph), 73.2 (C-5), 70.8 (C-3), 70.5 (Fmoc-CH2), 69.3
(C-6), 56.6 (C-2), 46.7 (Fmoc-CH), 37.8 (CH2), 29.6 (CH2), 28.1
(COCH3), 25.5 [SiC(CH3)3], 17.8 [SiC(CH3)3], 8.9 (DMM-CH3),
–4.0, –5.4 (2ϫ SiCH3) ppm. ESI-HRMS (positive mode): calcd.
for [C45H53NO11Si+Na]+ 834.3280; found 834.3255.
silyl 6-O-Benzyl-2-deoxy-2-dimethylmaleimido-4-O-phenoxyacetyl-
β- -glucopyranoside (5b): The regioisomeric mixture obtained from
D
4ba after General Procedure D was purified by column chromatog-
raphy to give 3b/5b = 60:40 (0.34 g, 85%). The physical and analyti-
cal data were found to be the same as given above.
tert-Butyldimethylsilyl 6-O-Benzyl-2-deoxy-2-dimethylmaleimido-3-
O-phenoxyacetyl-β-
silyl 6-O-Benzyl-2-deoxy-2-dimethylmaleimido-4-O-phenoxyacetyl-
β- -glucopyranoside (5b): The regioisomeric mixture obtained from
pure 3b after General Procedure D indicated 3b/5b = 60:40 by H
NMR of the crude reaction mixture.
D-glucopyranoside (3b) and tert-Butyldimethyl-
tert-Butyldimethylsilyl 3-O-Allyloxycarbonyl-6-O-benzyl-2-deoxy-2-
dimethylmaleimido-4-O-(9-fluorenylmethoxycarbonyl)-β-D-glucopyr-
D
anoside (4da): The residue obtained from 3d after General Pro-
cedure A was purified by column chromatography (petroleum
ether/ethyl acetate, 9:1) to give 4da (0.304 g, 88%) as a foam. Rf =
0.48 (petroleum ether/ethyl acetate, 8:2). [α]2D2 = –3.7 (c = 1.0,
1
tert-Butyldimethylsilyl 6-O-Benzyl-2-deoxy-2-dimethylmaleimido-β-
1
D-glucopyranoside (6): NaOMe/MeOH (1 , 118 µL) was added to
CHCl3). H NMR (400 MHz, CDCl3): δ = 7.63 (d, J = 7.6 Hz, 2
a solution of compound 4ab or 4ba (0.20 g, 0.236 mmol) in
CH2Cl2/MeOH (24 mL, 4:1), and the resulting reaction mixture
was stirred at room temp. for 2 h. The reaction mixture was neu-
tralized with IRA-120 and filtered through a plug of cotton. All
washings were concentrated under reduced pressure to give a resi-
due, and the residue was purified by column chromatography to
give 6 (0.11 g, 95%), as a viscous liquid. Rf = 0.33 (petroleum ether/
ethyl acetate, 1:1). [α]2D2 = –21.43 (c = 0.7, CHCl3). 1H NMR
(400 MHz, CDCl3): δ = 7.33–7.18 (m, 5 H, Ar-H), 5.16 (d, J =
8.0 Hz, 1 H, 1-H), 4.54 (ABq, J = 12.1 Hz, 2 H, OCH2Ph), 4.14
(dd, J = 10.6, 8.1 Hz, 1 H, 3-H), 3.77 (dd, J = 10.1, 8.1 Hz, 1 H,
2-H), 3.73–3.65 (m, 2 H, 6-Hab), 3.55–3.38 (m, 3 H, 4-H/5-H/OH),
3.16–2.93 (br. s, 1 H, OH), 1.87 (s, 6 H, DMM-CH3), 0.70 [s, 9 H,
SiC(CH3)3], –0.00 (s, 3 H, SiCH3), –0.08 (s, 3 H, SiCH3) ppm. 13C
NMR (101 MHz, CDCl3): δ = 172.3 (CO), 138.0, 137.4, 128.7,
128.0, 127.9 (Ar-C), 93.6 (C-1), 74.1, 74.0 (C-4/C-5), 73.9
(OCH2Ph), 71.7 (C-3), 70.7 (C-6), 58.4 (C-2), 25.5 [SiC(CH3)3],
17.8 [SiC(CH3)3], 8.8 (DMM-CH3), –4.0, –5.4 (2ϫ SiCH3) ppm.
ESI-HRMS (positive mode): calcd. for [C25H37NO7Si+Na]+
514.2232; found 514.2214.
H, Ar-H), 7.44 (dd, J = 12.0, 7.5 Hz, 2 H, Ar-H), 7.28 (d, J =
1.8 Hz, 2 H, Ar-H), 7.24–7.13 (m, 6 H, Ar-H), 7.11 (d, J = 9.9 Hz,
1 H, Ar-H), 5.62–5.51 (m, 1 H, HC=CH2), 5.57 (dd, J = 10.9,
9.1 Hz, 1 H, 3-H), 5.30 (d, J = 8.0 Hz, 1 H, 1-H), 4.99 (dd, J =
17.3, 1.4 Hz, 1 H, HC=CH2), 4.93 (t, J = 9.6 Hz, 1 H, 4-H), 4.90
(dd, J = 10.4, 1.2 Hz, 1 H, HC=CH2), 4.44 (ABq, J = 12.1 Hz, 2
H, OCH2Ph), 4.34 (dd, J = 13.2, 5.6, = Hz, 1 HCHCHHO–), 4.30–
4.22 (m, 2 H, =CHCHHO–/Fmoc-CHH), 4.10 (dd, J = 9.9, 7.5 Hz,
1 H, Fmoc-CHH), 4.04 (t, J = 7.5 Hz, 1 H, Fmoc-CH), 4.03 (dd,
J = 10.8, 8.0 Hz, 1 H, 2-H), 3.80 (dt, J = 9.9, 4.2 Hz, 1 H, 5-H),
3.57 (d, J = 4.2 Hz, 2 H, 6-Hab), 1.83 (s, 6 H, DMM-CH3), 0.68
[s, 9 H, SiC(CH3)3], –0.00 (s, 3 H, SiCH3), –0.09 (s, 3 H, SiCH3)
ppm. 13C NMR (101 MHz, CDCl3): δ = 154.4, 154.3 (2ϫ OCO),
143.4, 143.2, 141.3, 138.0, 137.49, 131.3 (HC=CH2), 128.4, 128.0,
127.7, 127.6, 127.3, 127.3, 125.3, 125.3, 120.1, 120.1 (Ar-C), 118.5
(HC=CH2), 93.3 (C-1), 74.7 (C-3), 74.3 (C-4), 73.6 (OCH2Ph), 72.9
(C-5), 70.4 (Fmoc-CH2), 69.3 (C-6), 68.7 (OCH2CH=CH2), 56.6
(C-2), 46.7 (Fmoc-CH), 25.4 [C(CH3)3], 17.7 [C(CH3)3], 8.8
(DMM-CH3), –4.1, –5.5 (2 ϫ SiCH3) ppm. ESI-MS (positive
mode): calcd. for [C44H51NO11Si+Na]+ 820.3124; found 820.3091.
C44H51NO11Si (797.96): calcd. C 66.23, H 6.44, N 1.76; found C
65.80, H 6.25, N 1.76.
tert-Butyldimethylsilyl 6-O-Benzyl-2-deoxy-2-dimethylmaleimido-4-
O-levulinoyl-β-D-glucopyranoside (5c) and tert-Butyldimethylsilyl 6-
tert-Butyldimethylsilyl 6-O-Benzyl-2-deoxy-2-dimethylmaleimido-4-
O-Benzyl-2-deoxy-2-dimethylmaleimido-3-O-levulinoyl-β-
D
-gluco-
O-phenoxyacetyl-β-
silyl 6-O-Benzyl-2-deoxy-2-dimethylmaleimido-3-O-phenoxyacetyl-
β- -glucopyranoside (3b): The regioisomeric mixture obtained from
D
-glucopyranoside (5b) and tert-Butyldimethyl-
pyranoside (3c): The residue obtained from 4ac after General Pro-
cedure D (with piperidine) was purified by column chromatography
to give 5c/3c (82:18, 53 mg, 86%) as a thick liquid. The residue
obtained from 4ac after General Procedure D (with triethylamine)
was purified by column chromatography to give 5c (0.052 g, 84%)
as a viscous liquid. Rf = 0.24 (petroleum ether/ethyl acetate, 1:1).
D
4ab after General Procedure D was separated by column
chromatography. Initial elution with petroleum ether/ethyl acetate
(9:1) afforded 5b (684 mg, 53%) as a viscous liquid. The physical
and analytical data were found to be the same as given above. Fur- [α]2D2 = +3.1 (c = 1.0, CHCl3). 1H NMR (400 MHz, CDCl3): δ =
ther elution with petroleum ether/ethyl acetate (8.5:1.5) afforded 3b
(458 mg, 36%) as a viscous liquid. Rf = 0.55 (petroleum ether/ethyl
7.34–7.23 (m, 5 H, Ar-H), 5.24 (d, J = 8.1 Hz, 1 H, 1-H), 4.89 (t,
J = 9.4 Hz, 1 H, 4-H), 4.53 (ABq, J = 12.4 Hz, 2 H, OCH2Ph),
acetate, 7:3). 1H NMR (400 MHz, CDCl3): δ = 7.24–7.11 (m, 7 H, 4.36 (t, J = 9.4 Hz, 1 H, 3-H), 3.91 (dd, J = 10.7, 8.2 Hz, 1 H, 2-
Ar-H), 6.87 (t, J = 7.4 Hz, 1 H, Ar-H), 6.75 (d, J = 8.0 Hz, 2 H,
Ar-H), 5.16 (d, J = 8.0 Hz, 1 H, 1-H), 4.98 (t, J = 9.5 Hz, 1 H, 4-H),
4.42 (ABq, J = 16.2 Hz, 2 H, PhOCH2), 4.39 (ABq, J = 12.0 Hz, 2
H, OCH2Ph), 4.29 (dd, J = 10.4, 9.5 Hz, 1 H, 3-H), 3.88 (dd, J =
H), 3.76–3.67 (m, 1 H, 5-H), 3.62–3.52 (m, 2 H, 6-Hab), 2.97–2.83
(br. s, 1 H, OH), 2.82–2.62 (m, 2 H, CH2), 2.54–2.32 (m, 2 H, CH2),
2.12 (s, 3 H, COCH3), 1.92 (s, 6 H, DMM-CH3), 0.75 [s, 9 H,
SiC(CH3)3], 0.06 (s, 3 H, SiCH3), –0.03 (s, 3 H, SiCH3) ppm. 13C
11.0, 8.1 Hz, 1 H, 2-H), 3.67–3.60 (m, 1 H, 5-H), 3.48–3.38 (m, 2 NMR (101 MHz, CDCl3): δ = 207.6 (COCH3), 172.9, 172.1 (2ϫ
H, 6-Hab), 3.01–2.68 (br. s, 1 H, OH), 1.81 (s, 6 H, DMM-CH3), CO), 138.4, 137.3, 130.0, 128.5, 127.8, 127.7 (Ar-C), 93.6 (C-1),
5008
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© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 5002–5011

Temporary Carbohydrate Diol Protection with Ester Groups
73.7 (C-4), 73.6 (OCH2Ph), 73.5 (C-5), 70.3 (C-3), 69.6 (C-6), 58.7 after General Procedure D was purified by column chromatog-
(C-2), 38.5 (CH2), 29.9 (COCH3), 28.3 (CH2), 25.6 [SiC(CH3)3], raphy to give 5a (160 mg, 88%) as a viscous liquid. The physical
17.8 [SiC(CH3)3], 8.9 (DMM-CH3), –4.0, –5.4 (2ϫ SiCH3) ppm.
ESI-HRMS (positive mode): calcd. for [C30H43NO9Si+Na]+
612.2599; found 612.2579.
and analytical data were found to be the same as given above.
tert-Butyldimethylsilyl 6-O-Benzyl-2-deoxy-2-dimethylmaleimido-4-
O-(9-fluorenylmethoxycarbonyl)-β-D-glucopyranoside (5a): Dime-
tert-Butyldimethylsilyl 6-O-Benzyl-2-deoxy-2-dimethylmaleimido-3-
O-(9-fluorenylmethoxycarbonyl)-β-D-glucopyranoside (3a): Hydraz-
done (0.133 g, 0.952 mmol), followed by Pd(PPh3)4 (2.0 mg,
0.0125 mmol), were added under a counter flow of Ar to a solution
of 4da (100 mg, 0.125 mmol) in degassed THF (3 mL), and the
resulting reaction mixture was stirred under Ar for 30 min. The
reaction mixture was diluted with ethyl acetate and concentrated
under reduced pressure to give a residue. Column chromatographic
purification of the residue afforded 5a (76 mg, 85%) as a viscous
liquid. Rf = 0.39 (petroleum ether/ethyl acetate, 7:3). [α]2D2 = +0.86
(c = 0.7, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 7.76 (d, J =
7.5 Hz, 2 H, Ar-H), 7.56 (dd, J = 6.6, 6.1 Hz, 2 H, Ar-H), 7.40 (t,
J = 7.3 Hz, 2 H, Ar-H), 7.34–7.18 (m, 7 H, Ar-H), 5.26 (d, J =
ine acetate (11 mg, 126 µmol) was added to a solution of 4ac
(85 mg, 105 µmol) in CH2Cl2/MeOH (9:1; 1 mL), and the resulting
reaction mixture was stirred at room temp. for 25 min. Volatiles
were removed under reduced pressure to give a viscous mass, which
was purified by column chromatography to give 3a (61 mg, 82%)
as a foam. The physical and analytical data were found to be the
same as given above.
tert-Butyldimethylsilyl 6-O-Benzyl-2-deoxy-2-dimethylmaleimido-3-
O-levulinoyl-β-D-glucopyranoside (3c) and tert-Butyldimethylsilyl 6-
O-Benzyl-2-deoxy-2-dimethylmaleimido-4-O-levulinoyl-β-D-glucopyr- 8.0 Hz, 1 H, 1-H), 4.78 (t, J = 9.4 Hz, 1 H, 4-H), 4.56 (ABq, J =
anoside (5c): The residue obtained from 4ca after General Pro-
cedure D (with piperidine) indicated 3c/5c = 93:7 by H NMR of
12.2 Hz, 2 H, OCH2Ph), 4.45 (t, J = 10.1 Hz, 1 H, 3-H), 4.39 (dd,
J = 10.4, 7.4 Hz, 1 H, Fmoc-CHH), 4.33 (dd, J = 10.4, 7.3 Hz, 1
H, Fmoc-CHH), 4.19 (app. t, J = 7.3 Hz, 1 H, Fmoc-CH), 3.94
(dd, J = 10.9, 8.1 Hz, 1 H, 2-H), 3.78 (dt, J = 9.8, 4.0 Hz, 1 H, 5-
H), 3.66 (d, J = 4.0 Hz, 2 H, 6-Hab), 2.50–2.31 (br. s, 1 H, OH),
1.95 (s, 6 H, DMM-CH3), 0.78 [s, 9 H, SiC(CH3)3], 0.09 (s, 3 H,
SiCH3), –0.00 (s, 3 H, SiCH3) ppm. 13C NMR (101 MHz, CDCl3):
δ = 172.1 (CO), 155.4 (OCO), 143.4, 143.4, 141.5, 141.5, 138.2,
137.4, 128.5, 128.1, 127.7, 127.7, 127.4, 127.4, 125.4, 125.3, 120.3
(Ar-C), 93.6 (C-1), 76.9 (C-4), 73.7 (OCH2Ph), 73.3 (C-5), 70.5 (C-
3), 70.3 (Fmoc-CH2), 69.4 (C-6), 59.1 (C-2), 46.8 (Fmoc-CH), 25.5
[SiC(CH3)3], 17.8 [SiC(CH3)3], 8.9 (DMM-CH3), –4.0, –5.4 (2ϫ
S iCH3 ) pp m. ES I- HR MS (p os it ive m od e) : c al cd . for
[C40H47NO9Si+Na]+ 736.2812; found 736.2868.
1
the crude reaction mixture. General procedure D (with triethyl-
1
amine) indicated 3c/5c (Ͼ 99:1) by H NMR spectroscopy of the
crude reaction mixture.
tert-Butyldimethylsilyl 6-O-Benzyl-2-deoxy-2-dimethylmaleimido-4-
O-(9-fluorenylmethoxycarbonyl)-β-D-glucopyranoside (5a): Hydraz-
ine acetate (4.1 mg, 44.3 µmol) was added to a solution of 4ca
(30 mg, 36.9 µmol) in CH2Cl2/MeOH (9:1; 1 mL), and the resulting
reaction mixture was stirred at room temp. for 16 h. Volatiles were
removed under reduced pressure and co-evaporated with toluene
(1 mL ϫ3) to give a viscous mass of 5a, which was vacuum-dried
for 3 h and confirmed by NMR spectroscopy.
tert-Butyldimethylsilyl 4-O-Allyloxycarbonyl-6-O-benzyl-2-deoxy-2-
dimethylmaleimido-β-D-glucopyranoside (5d): The residue obtained
tert-Butyldimethylsilyl 6-O-Benzyl-2-deoxy-2-dimethylmaleimido-4-
after General Procedure D was purified by column chromatog-
raphy to give 5d (18 mg, 89%) as a viscous liquid. Rf = 0.35 (petro-
leum ether/ethyl acetate, 7:3). [α]2D2 = –2.4 (c = 1.0, CHCl3). 1H
O-(9-fluorenylmethoxycarbonyl)-β-
Butyldimethylsilyl 6-O-Benzyl-2-deoxy-2-dimethylmaleimido-3-O-
(9-fluorenylmethoxycarbonyl)-β- -glucopyranoside (3a): p-Tol-
D-glucopyranoside (5a) and tert-
D
NMR (400 MHz, CDCl3): δ = 7.37–7.25 (m, 5 H, Ar-H), 5.94–5.80 SO2Na (60 mg, 340 µmol) and Pd(PPh3)4 (5.4 mg, 34 µmol) were
(m, 1 H, HC=CH2), 5.33 (dd, J = 17.4, 1.4 Hz, 1 H, HC=CH2), added under a counter flow of Ar to a solution of 4da (274 mg,
5.26 (dd, J = 10.4, 1.1 Hz, 1 H, HC=CH2), 5.25 (d, J = 8.0 Hz, 1 340 µmol) in degassed and dry THF/MeOH (2:1; 3 mL). After 1 h,
H, 1-H), 4.77 (t, J = 9.4 Hz, 1 H, 4-H), 4.59 (m, 4 H, OCH2Ph,
OCH2CH=), 4.41 (dd, J = 10.9, 9.1 Hz, 1 H, 3-H), 3.94 (dd, J =
11.0, 8.0 Hz, 1 H, 2-H), 3.75 (dt, J = 9.9, 4.0 Hz, 1 H, 5-H), 3.67
(d, J = 4.0 Hz, 2 H, 6-Hab), 2.52–2.06 (br. s, 1 H, OH), 1.95 (s, 6
H, DMM-CH3), 0.78 [s, 9 H, SiC(CH3)3], 0.09 (s, 3 H, SiCH3),
0.00 (s, 3 H, SiCH3) ppm. 13C NMR (101 MHz, CDCl3): δ = 172.1
(CO), 155.2 (OCO), 138.2, 137.4, 131.3 (HC=CH2), 128.7, 128.5,
127.9, 127.7, 127.7 (Ar-C), 119.5 (HC=CH2), 93.6 (C-1), 77.1 (C-
4), 73.7 (OCH2Ph), 73.3 (C-5), 70.3 (C-3), 69.3, 69.2 (OCH2CH = /
C-6), 59.0 (C-2), 25.5 [SiC(CH3)3], 17.8 [SiC(CH3)3], 8.9 (DMM-
CH3), –4.0, –5.4 (2ϫ SiCH3) ppm. ESI-HRMS (positive mode):
calcd. for [C29H41NO9Si+Na]+ 598.2443; found 598.2427.
the pale yellow reaction mixture was diluted with ethyl acetate
(5 mL), and volatiles were removed under reduced pressure to give
a residue. Column chromatographic purification of the residue af-
forded 5a (79 mg, 33%) and 3a (65 mg, 27%) as foams.
tert-Butyldimethylsilyl 4,6-O-Benzylidene-2-deoxy-2-dimethylmale-
imido-3-O-naphthylmethyl-β-D-glucopyranoside (2e): TMSOTf
(20 µL, 107 µmol) was added dropwise to a solution of compound
1 (5.22 g, 10.67 mmol) in diethyl ether (25 mL), and the mixture
was stirred at room temp. for 10 min. NapOTCA (4.48 g,
14.94 mmol) in Et2O (35 mL) was injected over a period of 30 min.
Additional TMSOTf (20 µL, 107 µmol) was injected, and the mix-
ture was stirred for 10 min. The reaction mixture was neutralized
with triethylamine (1 mL) and concentrated under reduced pressure
to give a residue. The residue was purified by column chromatog-
raphy (petroleum ether/ethyl acetate, 9:1) to give 2e (4.44 g, 66%)
as a white solid. M.p. 148–149 °C; Rf = 0.66 (petroleum ether/ethyl
tert-Butyldimethylsilyl 6-O-Benzyl-2-deoxy-2-dimethylmaleimido-3-
O-(9-fluorenylmethyoxycarbonyl)-β-D-glucopyranoside (3a): Dime-
done (107 mg, 762 µmol), followed by Pd(PPh3)4 (1.6 mg, 10 µmol),
were added under a counter flow of Ar to a solution of 4ad (80 mg,
100 µmol) in degassed THF (2 mL), and the resulting reaction mix-
ture was stirred under Ar for 90 min. The reaction mixture was
diluted with ethyl acetate and concentrated under reduced pressure
to give a residue. Column chromatographic (petroleum ether/ethyl
acetate, 8:2) purification of the residue afforded 3a (64 mg, 89%)
as a foam.
1
acetate, 8:2). [α]2D2 = +59.6 (c = 1.0, CHCl3). H NMR (400 MHz,
CDCl3): δ = 7.81–7.69 (m, 2 H, Ar-H), 7.66 (d, J = 8.4 Hz, 1 H,
Ar-H), 7.57 (m, 3 H, Ar-H), 7.51–7.32 (m, 5 H, Ar-H), 7.28 (dd, J
= 8.4, 1.4 Hz, 1 H, Ar-H), 5.62 (s, 1 H, CHPh), 5.26 (d, J = 8.1 Hz,
1 H, 1-H), 5.00 (d, J = 12.8 Hz, 1 H, OCHAr), 4.63 (d, J = 12.8 Hz,
1 H, OCHAr), 4.40 (dd, J = 10.3, 9.0 Hz, 1 H, 3-H), 4.35 (dd, J =
tert-Butyldimethylsilyl 3-O-Allyloxycarbonyl-6-O-benzyl-2-deoxy-2- 10.4, 5.4 Hz, 1 H, 6-Ha), 3.97 (dd, J = 10.4, 8.1 Hz, 1 H, 2-H),
dimethylmaleimido-β- -glucopyranoside (3d): The residue obtained 3.84 (dd, J = 10.4, 9.8 Hz, 1 H, 6-Hb), 3.79 (t, J = 9.0 Hz, 1 H, 4-
D
Eur. J. Org. Chem. 2009, 5002–5011
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5009

S. D. Markad, R. R. Schmidt
FULL PAPER
H), 3.62 (dt, J = 9.8, 4.9 Hz, 1 H, 5-H), 1.92–1.48 (s, 3 H, DMM-
CH3), 1.39–1.02 (s, 3 H, DMM-CH3), 0.75 [s, 9 H, SiC(CH3)3],
0.04 (s, 3 H, SiCH3), –0.08 (s, 3 H, SiCH3) ppm. 13C NMR
was diluted by addition of satd. NaHCO3 (3 mL), and volatiles
were removed under reduced pressure. The resulting solution was
extracted with CH2Cl2 (5 mL ϫ3) and worked up. The residue was
(101 MHz, CDCl3): δ = 171.4 (CO), 137.6, 136.5, 136.1, 133.2, purified by column chromatography to give 5a (65 mg, 78%) as a
132.9, 129.1, 128.3, 128.1, 127.9, 127.5, 127.3, 126.7, 126.2, 126.2,
126.0 (Ar-C), 101.4 (PhCH), 94.0 (C-1), 83.0 (C-4), 75.5 (C-3), 74.5
(OCH2Ar), 68.8 (C-6), 66.3 (C-5), 57.9 (C-2), 25.4 [SiC(CH3)3],
17.6 [SiC(CH3)3], 7.8 (DMM-CH3), –4.2, –5.6 (2ϫ SiCH3) ppm.
ESI-HRMS (positive mode): calcd. for [C36H43NO7Si+Na]+
652.2701; found 652.2673.
foam. The physical and analytical data were found to be the same
as given above.
tert-Butyldimethylsilyl 6-O-Benzyl-2-deoxy-2-dimethylmaleimido-3-
O-naphthylmethyl-β-D-glucopyranoside (3e): The residue obtained
after General Procedure D gave 2e (75 mg, 86%) as a white solid.
The physical and analytical data were the same as given above.
tert-Butyldimethylsilyl 6-O-Benzyl-2-deoxy-2-dimethylmaleimido-3-
O-naphthylmethyl-β-D-glucopyranoside (3e): The residue obtained
Supporting Information (see footnote on the first page of this arti-
cle): NMR spectra for all new compounds.
from 2e after General Procedure C was purified by column
chromatography (petroleum ether/ethyl acetate, 8:2) to afford 3e
(2.4 g, 89%) as a viscous syrup. Rf = 0.55 (petroleum ether/ethyl
acetate, 7:3). [α]2D2 = +28.60 (c = 1.0, CHCl3). 1H NMR (400 MHz,
CDCl3): δ = 7.86 (dd, J = 6.1, 2.9 Hz, 2 H, Ar-H), 7.76 (d, J =
8.4 Hz, 1 H, Ar-H), 7.68 (s, 1 H, Ar-H), 7.58–7.50 (m, 2 H, Ar-H),
7.48–7.36 (m, 6 H, Ar-H), 5.26 (d, J = 8.1 Hz, 1 H, 1-H), 5.11 (d,
J = 12.8 Hz, 1 H, OCHAr), 4.73 (d, J = 12.8 Hz, 1 H, OCHAr),
4.70 (ABq, J = 11.8 Hz, 2 H, OCH2Ph), 4.29 (dd, J = 10.8, 8.5 Hz,
1 H, 3-H), 3.96 (dd, J = 10.7, 8.1 Hz, 1 H, 2-H), 3.93–3.84 (m, 3
H, 4-H/6-Hab), 3.71 (dt, J = 9.7, 4.8 Hz, 1 H, 5-H), 3.36–3.23 (br.
s, 1 H, OH), 1.82–1.55 (br. s, 3 H, DMM-CH3), 1.45–1.15 (br. s, 3
H, DMM-CH3), 0.80 [s, 9 H, SiC(CH3)3], 0.11 (s, 3 H, SiCH3),
–0.00 (s, 3 H, SiCH3) ppm. 13C NMR (101 MHz, CDCl3): δ =
172.1, 171.4 (2 ϫ CO), 137.9, 136.5, 133.3, 132.9, 129.2, 128.6,
128.4, 128.2, 128.1, 127.9, 127.8, 127.6, 126.9, 126.5, 126.3, 126.0,
125.4 (Ar-C), 93.6 (C-1), 80.0 (C-3), 74.9 (OCH2Ph), 74.4 (C-4),
73.9 (s, C-5/OCH2Ar), 70.9 (C-6), 57.5 (C-2), 25.4 [SiC(CH3)3], 17.7
[SiC(CH3)3], 8.4, 7.6 (DMM-CH3), –4.1, –5.5 (2ϫ SiCH3) ppm.
ESI-HRMS (positive mode): calcd. for [C36H45NO7Si+Na]+
654.2858; found 654.2832.
Acknowledgments
This work was supported by the University of Konstanz, the Alex-
ander von Humboldt Foundation and the Fonds der Chemischen
Industrie. S. D. M. is particularly grateful for a Humboldt fellow-
ship. The authors thank Ms. Anna-Lena Steck for her help in meas-
uring HR masses.
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4437.
tert-Butyldimethylsilyl 6-O-Benzyl-2-deoxy-2-dimethylmaleimido-4-
O-(9-fluorenylmethoxycarbonyl)-3-O-naphthylmethyl-β-D-glucopyr-
anoside (4ea): The residue obtained from 3e after General Pro-
cedure A was purified by column chromatography to give 4ea
(2.77 g, 84%) as a viscous oil. Rf = 0.50 (petroleum ether/ethyl
1
acetate, 8:2). [α]2D2 = +52.8 (c = 1.0, CHCl3). H NMR (400 MHz,
CDCl3): δ = 7.73–7.62 (m, 4 H, Ar-H), 7.60–7.45 (m, 4 H, Ar-H),
7.43–7.35 (m, 2 H, Ar-H), 7.34–7.14 (m, 10 H, Ar-H), 5.13 (d, J =
8.1 Hz, 1 H, 1-H), 4.95–4.87 (dd, J = 9.6, 9.4 Hz, 1 H, 4-H), 4.77
(d, J = 12.8 Hz, 1 H, OCHHAr), 4.50 (s, 2 H, OCH2Ph), 4.40–4.26
(m, 4 H, Fmoc-CH2/OCHHAr/3-H), 4.09 (t, J = 7.0 Hz, 1 H,
Fmoc-CH), 3.90 (dd, J = 10.8, 8.1 Hz, 1 H, 2-H), 3.75 (dt, J =
10.1, 4.0 Hz, 1 H, 5-H), 3.66–3.57 (m, 2 H, 6-Hab), 1.65–1.40 (br.
s, 3 H, DMM-CH3), 1.28–0.97 (br. s, 3 H, DMM-CH3), 0.67 [s, 9
H, SiC(CH3)3], –0.00 (3 H, s SiCH3), –0.13 (3 H, s SiCH3) ppm.
13C NMR (101 MHz, CDCl3): δ = 154.5 (CO), 143.4, 143.2, 141.4,
141.4, 138.2, 136.5, 136.0, 133.1, 132.9, 128.4 (s), 128.1, 128.0,
128.0, 127.6 (s), 127.6, 127.5, 127.3, 127.2, 126.8, 126.5, 126.3,
126.1, 125.1, 125.1, 120.2 (Ar-C), 93.5 (C-1), 77.9 (C-3), 77.4 (C-
4), 74.6 (OCH2Ar), 73.6 (OCH2Ph), 73.1 (C-5), 69.9 (s, Fmoc-CH2/
C-6), 57.6 (C-2), 46.8 (Fmoc-CH), 25.4 [SiC(CH3)3], 17.6
[SiC(CH3)3], 7.6 (DMM-CH3), –4.1, –5.6 (2ϫ SiCH3) ppm. ESI-
HRMS (positive mode): calcd. for [C51H55NO9Si+Na]+ 876.3538;
found 876.3496.
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tert-Butyldimethylsilyl 6-O-Benzyl-2-deoxy-2-dimethylmaleimido-4-
O-(9-fluorenylmethoxycarbonyl)-β-D-glucopyranoside (5a): DDQ
(81 mg, 357 µmol) was added to a solution of 4ea (100 mg,
119 µmol) in CH2Cl2/MeOH (4:1; 5 mL), and the resulting reaction
mixture was stirred at room temp. for 2 h. The reaction mixture
5010
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Eur. J. Org. Chem. 2009, 5002–5011

Temporary Carbohydrate Diol Protection with Ester Groups
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Published Online: September 2, 2009
Eur. J. Org. Chem. 2009, 5002–5011
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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